The study consists of two parts: dose escalation and recommended phase 2 dose expansion. Each
part of the study will include two separate groups of participants. Group A will include
participants who will have cutaneous/subcutaneous tumors injected, and group B will include
participants who will have visceral tumors injected. The study will consist of the following
periods: screening, initial treatment period (two 28 day cycles), optional extended treatment
period (continued 28 day cycles) and a follow up period (safety and survival follow up).
Inclusion Criteria:
- Subject must have histologically- or cytologically-confirmed diagnosis of advanced or
metastatic solid tumor(s).
- Subject has measurable disease as determined by Response Evaluation Criteria in Solid
Tumors (RECIST) version 1.1. At least 1 lesion must be suitable for intratumoral (IT)
injection. Lesions for injection must be ≥ 10 mm and ≤ 60 mm in longest diameter.
- Subject has progressed on or is not eligible for available standard therapy.
- Subject has a predicted life expectancy ≥ 12 weeks.
- Subject has at least 2 sites of disease suitable for biopsy and is willing and able to
undergo required tumor biopsies according to the treating institution's guidelines at
screening and during study treatment.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- A female subject is eligible to participate if she is not pregnant and at least 1 of
the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment
period and for at least 180 days after the final study investigational product
(IP) administration.
- Female subject must agree not to breastfeed starting at screening, and throughout the
study period and 180 days after the final study IP administration.
- Female subject must not donate ova starting at screening, and throughout the study
period and for 180 days after the final study IP administration.
- Male subject must agree to remain abstinent or use a condom throughout the study
period and for 180 days after the final study IP administration.
- Male subject with female partner(s) of childbearing potential must agree to use
contraception during the treatment period and for at least 180 days after the final
study IP administration.
- Male subject must not donate sperm during the treatment period and for at least 180
days after the final study IP administration.
- Subject must be willing and able to comply with the study requirements including
prohibited concomitant medication restrictions.
- Subject agrees not to participate in another interventional study while receiving
study IP.
- Subject has the ability to understand and the willingness to sign a written informed
consent document.
Exclusion Criteria:
- Subject has ongoing toxicity ≥ Common Terminology Criteria for Adverse Events (CTCAE)
grade 2 attributable to prior antineoplastic therapies considered clinically
significant.
- Subject who has had major surgery ≤ 4 weeks of screening.
- Subject is concurrently participating in another interventional study or has received
an investigational product ≤ 30 days or 5 half-lives whichever is shorter, prior to
first IP administration.
- Subject with symptomatic or untreated central nervous system metastases or
leptomeningeal disease. Subjects with treated symptomatic brain metastases should be
neurologically stable (for 4 weeks post-treatment and prior to screening) and off
steroids for at least 2 weeks prior to first IP administration.
- Subject with active or prior autoimmune or inflammatory disorders requiring systemic
therapy within past 2 years (including inflammatory skin conditions or severe eczema,
inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (with
the exception of diverticulosis), celiac disease, systemic lupus erythematosus,
Sarcoidosis syndrome, Wegener syndrome (granulomatosis with polyangiitis), Graves'
disease, rheumatoid arthritis, hypophysitis, uveitis, etc.
The following are exceptions to this criterion:
- Subject with vitiligo or alopecia
- Subject with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone
replacement
- Any chronic skin condition that does not require systemic therapy
- Subject with another malignancy that currently requires treatment.
- Subject with tumors encasing major vascular structures such as the carotid
artery, tumors adjacent to vital neurovascular structures or tumors in locations
that are at high risk for adverse events (AEs) or otherwise not considered
appropriate for IT injection.
- Subject with inadequate organ and marrow functions meeting any of the below
criteria:
- Leukocytes < 3000/μL
- Absolute neutrophil count < 1500/μL
- Platelets < 100,000/μL
- Hemoglobin (Hgb) < 9 g/dL
- International normalized ratio (INR) > 1.5 × ULN and/or activated partial
thromboplastin time (aPTT) > 1.5 × institutional normal limits, except for patients in
Group B (Visceral Lesions) escalation and expansion groups where INR and aPTT must be
normal
- Total Bilirubin (TBL) > 1.5 × institutional normal limits (subjects with known Gilbert
syndrome who are excluded if TBL > 3.0 × institutional normal limits or direct
bilirubin > 1.5 × institutional normal limits)
- Aspartate aminotransferase (AST) and Alanine transaminase (ALT) > 3.0 × institutional
normal limits. Subjects with tumors in the liver AST and ALT > 5 × institutional
normal limits.
- Albumin < 3.4 g/dL
- Creatinine > 1.5 × institutional normal limits
- Subject with a condition requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone equivalents) or other immunosuppressive medications
within 14 days of first administration of study IP. Inhaled or topical steroids
and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted
in the absence of active autoimmune disease.
- Subject has an uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, any form of
substance abuse or psychiatric illness/social situations that would limit
compliance with study visits or requirements or a condition that could invalidate
communication with the investigator.
- Subject is known to be positive for human immunodeficiency virus, hepatitis B
surface antigen, hepatitis B core immunoglobulin or immunoglobulin G (IgG)
antibody or hepatitis C (IgG or ribonucleic acid (RNA) test) indicating acute or
chronic infection.
- Subject has a history of moderate to severe ascites, clinically significant
and/or rapidly accumulating ascites, bleeding esophageal varices, hepatic
encephalopathy or pericardial and/or pleural effusions related to liver
insufficiency within 6 months of screening. Mild ascites that does not preclude
safe IT injection of ASP9801 is allowed.
- Subject has a clinically significant abnormal electrocardiogram (ECG) at
screening.
- Subject has symptomatic cardiovascular disease within the preceding 12 months
unless cardiology consultation and clearance has been obtained for study
participation, including but not limited to the following: significant coronary
artery disease (e.g., requiring angioplasty or stenting), acute myocardial
infarction or unstable angina pectoris < 3 months prior to screening,
uncontrolled hypertension, clinically significant arrhythmia or congestive heart
failure (New York Heart Association grade ≥ 2).
- Subject has medical conditions that predispose the subject to untoward medical
risk in the event of volume loading (e.g., intravenous fluid bolus infusion),
tachycardia or hypotension during or following treatment with ASP9801.
- Subject has a known or suspected hypersensitivity to ASP9801 or any components of
the formulation used, including prior adverse reaction to vaccinia (e.g., as
smallpox vaccine).
- Subject has had previous exposure with ASP9801.
